The olive constituent oleuropein, as a PPARα agonist, markedly reduces serum triglycerides

Abstract

Oleuropein (OLE), a main constituent of olive, exhibits antioxidant and hypolipidemic effects, while it reduces the infarct size in chow- and cholesterol-fed rabbits. Peroxisome proliferator-activated receptor α (PPARα) has essential roles in the control of lipid metabolism and energy homeostasis. This study focused on the mechanisms underlying the hypolipidemic activity of OLE and, specifically, on the role of PPARα activation in the OLE-induced effect. Theoretical approach using Molecular Docking Simulations and luciferase reporter gene assay indicated that OLE is a ligand of PPARα. The effect of OLE (100 mg/kg, p.o., per day, ×6 weeks) on serum triglyceride (TG) and cholesterol levels was also assessed in adult male wild-type and Ppara-null mice. Molecular Docking Simulations, Luciferase reporter gene assay and gene expression analysis indicated that OLE is a PPARα agonist that up-regulates several PPARα target genes in the liver. This effect was associated with a significant reduction of serum TG and cholesterol levels. In contrast, OLE had no effect in Ppara-null mice, indicating a direct involvement of PPARα in the OLE-induced serum TG and cholesterol reduction. Activation of hormone-sensitive lipase in the white adipose tissue (WAT) and the liver of wild-type mice and up-regulation of several hepatic factors involved in TG uptake, transport, metabolism and clearance may also contribute in the OLE-induced TG reduction. In summary, OLE has a beneficial effect on TG homeostasis via PPARα activation. OLE also activates the hormone sensitive lipase in the WAT and liver and up-regulates several hepatic genes with essential roles in TG homeostasis.

Oleuropein: A natural antioxidant molecule in the treatment of metabolic syndrome

“…Furthermore, an in silico study showed that oleuropein was a PPAR‐α ligand that was corroborated with evidence of increased PPAR‐α and retinoid X receptor homodimerization. This same study also found that oleuropein upregulated the LDL‐R receptor in the liver and increased the expression of other genes involved in synthesis, uptake, transport, metabolism, and elimination of TGs (Malliou et al, ). This evidence suggests that oleuropein may have a similar mechanism of action for as of lipid‐lowering drugs fibrates, though potentially with relatively lesser risk of associated adverse effects.…”

“…Hadrich, Garcia, et al, 2016). In wild-type mice, oleuropein caused reduction in serum TG and TC but not in PPAR-α null mice showing that effect was due to activation and upregulation of PPAR-α mRNA with an increase in multiple PPAR-α target genes (Malliou et al, 2018). Furthermore, an in silico study showed that oleuropein was a PPAR-α ligand that was corroborated with evidence of increased PPAR-α and retinoid X receptor homodimerization.…”

“…Oleuropein has been shown to reduce serum LDL (Jemai et al, 2008; A. Mahmoudi et al, ; Khalili et al, ; Lepore et al, ; F. Hadrich, Garcia, et al, ), TC (Jemai et al, 2008; A. Mahmoudi et al, ; Khalili et al, ; I. Andreadou et al, ; F. Hadrich, Garcia, et al, ; 246, Y. Oi‐Kano et al, ), and serum triglycerides (Jemai et al, 2008; A. Mahmoudi et al, ; Khalili et al, ; I. Andreadou et al, ; F. Hadrich, Garcia, et al, ; Y. Oi‐Kano et al, ) while also increasing serum HDL (Jemai et al, 2008; A. Mahmoudi et al, ; Khalili et al, ; F. Hadrich, Garcia, et al, ). In wild‐type mice, oleuropein caused reduction in serum TG and TC but not in PPAR‐α null mice showing that effect was due to activation and upregulation of PPAR‐α mRNA with an increase in multiple PPAR‐α target genes (Malliou et al, ). Furthermore, an in silico study showed that oleuropein was a PPAR‐α ligand that was corroborated with evidence of increased PPAR‐α and retinoid X receptor homodimerization.…”

Hydroxytyrosol, Tyrosol and Derivatives and Their Potential Effects on Human Health

“…In vitro Ole exerts anti-adipogenic effect through inhibition of both expression and activity of PPARγ, essential for the formation and function of adipocytes [223,224]. Ole was shown to be a ligand of PPARα by molecular docking simulations and the effect of Ole was associated with a significant reduction of serum TG and cholesterol levels in mice [225]. In vivo experiments suggested that Ole exerts anti-obesity effects by regulating the expression of genes involved in adipogenesis in the visceral adipose tissue of HFD-fed mice [226].…”

FoodOmicsGR_RI: A Consortium for Comprehensive Molecular Characterisation of Food Products

“…Members of the FoodOmicsGR_RI consortium have investigated the health benefits of different constituents of emblematic Greek traditional foods like olive tree polyphenols for their cardioprotective, anti-ischemic and hypolipidemic effects [ 121 , 122 , 123 , 124 , 125 , 126 , 127 ] as well as their activity in combination with well-known chemotherapeutics [ 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 ]. The characterisation of foods’ constituents, quality or chemical markers and dereplication of known compounds are amongst our research axis and applications.…”